In 2015, more than 80,000 individuals using blood thinners like Xarelto and Eliquis were hospitalized due to an extreme bleeding side effect. Unlike Warfarin, these next-generation anticoagulants don’t offer an antidote.
Portola Pharmaceuticals has worked to manufacture a medication to reverse the life-threatening, uncontrollable bleeding. Known as AndexXa, the reversal agent has been moving through the Food and Drug Administration (FDA) approval process.
Bleeding Side Effect
Next-generation anticoagulants work by selectively inhibiting Factor Xa, a blood enzyme that assists in clotting. The newer blood thinners protect against stroke in patients with atrial fibrillation and prevent deep vein thrombosis (DVT) and pulmonary embolism. The medications are also prescribed after knee or hip replacement surgeries.
New-age blood thinners hit the market as alternatives to Warfarin, a traditional anticoagulant requiring regular maintenance of blood tests and diet restrictions. The next-generation blood thinners are prescribed to more than 6 million patients, with a growing number of individuals experiencing bleeding as a side effect.
Since 2010, more than 15,000 people have been hospitalized from bleeding side effects related to Xarelto, Eliquis or Pradaxa. Unfortunately, an estimated 2,500 people have died.
Bleeding linked to these anticoagulants is life-threatening. Because of the widespread unmet need, AndexXa is considered a breakthrough therapy by the FDA.
AndexXa is manufactured by Portola Pharmaceuticals, a company focusing on thrombosis and other hematologic diseases. AndexXa helps to reverse anticoagulation and stop bleeding caused by apixaban, rivaroxaban, edoxaban or enoxaparin.
AndexXa, also known as andexanet alfa, is a protein molecule that stops blood thinners from inhibiting Factor Xa. AndexXa could then return hemostatic processes to normal. AndexXa is the first Factor Xa inhibitor reversal agent of its kind.
In safety studies, such as the Phase 3 ANNEXA™ trial, AndexXa showed promising results. Data illustrated AndexXa “rapidly and substantially” stopped the extreme bleeding side effect caused by new-age blood thinners.
Within 12 hours, 79% of patients had the bleeding side effect reversed. The results were referred to as “excellent” or “good” during a presentation to the European Society of Cardiology in Rome.
More specifically, blood thinner Xarelto saw 89% decrease in Factor Xa activity when exposed to AndexXa. Xarelto is manufactured by Johnson & Johnson. Doctors also saw a 93% decrease of Factor Xa activity in patients using Bristol-Myers Squibb and Pfizer’s Eliquis.
In Oct. 2015, the Food and Drug Administration (FDA) granted accelerated approval to Praxbind, the first antidote for Boehringer Ingelheim’s anticoagulant Pradaxa. However, AndexXa is still moving through the process.
After clinical trials, Portola Pharmaceuticals applied for a Biologics License Application (BLA) to approve the drug. The FDA rejected the reversal agent in August 2016, citing manufacturing concerns. Portola Pharmaceuticals received a Complete Response Letter (CRL), which required additional data but did not question the drug’s effectiveness.
The CRL included the following necessary developments for the approval of AndexXa:
- Additional manufacturing information
- Additional data to support inclusion of edoxaban and enoxaparin in the label
- Finalization of clinical amendments review for Portola’s post-marketing commitments
While the additional requirements have led to a delay, Market Exclusive projects that the antidote will be approved in 2017.
Another inclination leading to approval projections is financing from other pharmaceutical companies. Portola Pharmaceutical has stepped into a $50 million loan agreement with Bristol-Myers Squibb Company and Pfizer Inc to continue to research and develop the antidote.
AndexXa has been regarded as a "universal anticoagulant antidote”. Portola Pharmaceuticals plans to resubmit the BLA for FDA approval sometime in 2017.